The genus Yersinia includes three pathogenic species: Yersinia pestis, Yersinia enterocolitica and Yersinia pseudotuberculosis, which are implicated in sub-lethal and lethal infections in animals and humans (Brubaker, 1991).
Y. pestis, the etiologic agent causing plague in humans, has been responsible for high mortality in several epidemics throughout human history and remains a current threat as a potential biological warfare agent. Currently, about 2000 global cases of plague are reported to the World Health Organization each year. Most of these cases are the bubonic form, usually a consequence of the transmission of bacteria to humans via bites from fleas that have previously fed on infected rodents, and cross-infection occurring from domestic and wild animal contacts, including guinea pigs (Gabastou et al., 2000), prairie dogs (CLARK, 1977, Rayor, 1985), squirrels and other small rodents (Smego et al., 1999) or larger mammals, such as cats (Doll et al., 1994), dogs (Gould et al., 2008, Orloski & Eidson, 1995, Chomel et al., 1994, Pashine et al., 1999, Giambartolomei et al., 1999, Wang et al., 2011a), coyotes (Smego et al., 1999) and lions (Wong et al., 2009). The trends in plague epidemiology are the increased transmission of plague from wild rodents to domestic animals (cats or dogs) as residential areas encroach on enzootic plague foci and from domestic animals to their owners and veterinarians (Rollins et al., 2003, Perry & Fetherston, 1997). Large reservoirs of Y. pestis still exist on all major inhabited continents, except Australia (Perry & Fetherston, 1997). The reservoir for Y. pestis includes a variety of small, warm-blooded mammals including mice, rats, squirrels, chipmunks, rabbits, voles and prairie dogs (Cynomys spp.) (Perry & Fetherston, 1997).
Recently, the main focus of plague vaccine research has been to develop subunit vaccines, in particular targeting LcrV and F1 antigens, which were found to efficiently protect rodent and cynomolgus macaque against bubonic and pneumonic plague and are well tolerated in humans (Anderson et al., 1998, Andrews et al., 1996, Heath et al., 1998, Leary et al., 1995, Simpson et al., 1990, Une & Brubaker, 1984, Williamson et al., 1995b, Williamson et al., 2005, Quenee et al., 2011). However, the subunit vaccine had insufficient and highly variable protection against plague in African Green monkeys (Quenee et al., 2011, Smiley, 2008a). Additionally, the usefulness of F1 as a protective antigen is not clear, since strains can cause plague (Winter et al., 1960). Therefore, vaccines composed of a limited number of antigens (F1 and/or LcrV) may not be able to protect against F1-negative strains (Winter et al., 1960) or strains harboring LcrV variants (Anisimov et al., 2010).
Yersiniosis, a diarrheal illness, is typically a self-limiting disease in humans, mainly caused by Y. enterocolitica and Y. pseudotuberculosis which are transmitted via fecal-oral route from soil, water and a variety of animal food sources (Brubaker, 1991, Bottone, 1997, Galindo et al., 2011). In the Netherlands in the 1990s, Y. enterocolitica was the third most common bacterial cause of diarrhea, after Campylobacter and Salmonella. In 2011, yersiniosis was the fourth most frequently reported zoonosis in the EU with an overall notification rate of 1.63 cases per 100,000 population. The case fatality rate of human yersiniosis was 0.02% in 2011. Y. enterocolitica was the most common species reported in human cases and was isolated from 98.4% of the confirmed cases. Yersiniosis is one of the three leading foodborne zoonoses in Lithuania, and the incidence of 12.86 per 100,000 population in Lithuania was the highest among European Union (EU) member states in 2010 (Team, 2013, Bucher et al., 2008). Additionally, high rates of infection have been described in New Zealand. The incidence was reported to be 87/100,000, making it more common than Salmonellosis. The majority of isolates were Y. enterocolitica serotype O:3. The estimates of the cost of output loss due to Yersiniosis in 2009 was 1.06 million dollars in New Zealand (Scott et al., 2000).
Several studies have linked outbreaks of human yersiniosis to the consumption of contaminated foods, including pork meat and vegetables, as well as water. Pigs are of particular importance in Yersinia spp. epidemiology, as they are the main carriers and source of human enteropathogenic Y. enterocolitica, especially bioserotype 4/O:3, and Y. pseudotuberculosis bioserotype 2/O:3. Y. pseudotuberculosis and Y. enterocolitica (O serotype) have been isolated from ovine abortion cases. Infection of ewes with Y. pseudotuberculosis can lead to abortion, stillbirth or birth of weak or healthy lambs. Infection with Y. enterocolitica resulted in placentitis and abortion, with subsequent normal pregnancies (Galindo et al., 2011). In 2000, USDA ERS (USDA Economic Research Service) estimated $6.9 billion/year for medical costs, productivity losses, and costs of premature deaths for diseases caused by common foodborne pathogens including enterica pathogenic Yersinia species (Hubbert, 1972). Besides human health risks, animal diarrheal disease due to food-safety related pathogens and other animal-specific pathogens remain an economically important cause of production loss to livestock producers (Vanantwerpen et al., 2014, Fondrevez et al., 2014, Giannitti et al., 2014, Longenberger et al., 2014, Bernardino-Varo et al., 2013, Karbe & Erickson, 1984, Corbel et al., 1992, Slee & Button, 1990).
Currently, there are no effective vaccines to control zoonotic Y. pestis transmission in wild rodents and prevent enteric Yersiniosis in swine and cattle. Here, several Y. pseudotuberculosis rationally designed attenuated constructions will provide the advantage of simultaneously priming humoral and cellular immune responses against many Yersinia antigens, thereby greatly enhancing the likelihood of broad-based protection against plague and Yersiniosis.